Cdk Inhibitor p27Kip1 and Hormone Dependence in Breast Cancer

Carlos L. Arteaga, Daniel Medina, Myles Brown, Richard Santer

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

p27Kip1 is an important regulator of the G1 to S transition. While a potent inhibitor of cyclin-dependent-kinase (Cdk)2, p27 is also involved in assembly of cyclin D/Cdk4 complexes. Although rarely mutated, p27 is functionally downregulated in many human cancers by mechanisms involving enhanced degradation, cytoplasmic mislocalization, and/or sequestration by cyclin D/Cdk complexes in response to oncogenic signals. Therefore, low levels and/or cytoplasmic localized p27 have been associated with enhanced malignancy and poor patient prognosis in many neoplasias including breast cancer. Recent data discussed below suggest that a threshold of p27 is required for response to antiestrogens and, conversely, that low levels predict for antiestrogen resistance. These results imply that hormone receptor-positive tumors with low and/or cytosolic p27 respond poorly to antiestrogens and should be considered for alternative therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)368s-371s
JournalClinical Cancer Research
Volume10
Issue number1 II
DOIs
StatePublished - Jan 28 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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